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Pancreatic cancer: challenges and opportunities. Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with increasing incidence. The mortality rate of pancreatic cancer is rising rapidly, and is projected to be the second most common of all malignant tumors by 2030. However, the diagnosis and therapy of pancreatic cancer remain a formidable challenge. Recently, enormous efforts have been made to develop several new methods for the early diagnosis and treatment of pancreatic cancer. We briefly introduce the most groundbreaking advances in pancreatic cancer diagnosis and clinical treatment strategies over the past 15 years, including surgery, chemotherapy, endoscopic therapy, immunotherapy and personalized medicine. The signaling pathways that are altered in the progression of pancreatic cancer, which may be used as therapeutic targets, are also discussed.